The aim of this application is to study the function of the newly discovered mouse gene Foxi3 during development of the craniofacial sensory organs. All craniofacial sensory organs derive from a pan-placodal domain which surrounds the neural plate. Much of the pan-placodal domain is believed to be competent to give rise to each craniofacial sensory organ and is specified by receiving signals from neighboring tissues such as the neural plate, mesoderm and endoderm. Since the beginning of the 20th century, a number of craniofacial birth defects have been identified. Many of these present as multiple defects in craniofacial organs. In addition, recent studies have shown that zebrafish foxi1 is required for otic and jaw development. Thus, we hypothesize that mouse Foxi3 plays crucial roles during craniofacial development. Here, we propose to test this hypothesis in the following specific aims: 1) To determine the lineage of the descendants of Foxi3-expressing cells during cranial placode development. We will generate Foxi3-Cre BAG transgenic mice and mate them with Cre-loxP reporter mice. 2) To assess the loss-of-function of Foxi3 in placodal cell fate specification. We will generate Foxi3 knockout mice. 3) To assess the necessity of the down-regulation of Foxi3 in otic placode specification. We will generate floxed "stop"+Foxi3 transgenic mice and mate them with the Pax2-Cre mice. This project has significant potential for the future study of craniofacial and sensory organ development that will shed light on the genetic mechanisms of craniofacial birth defects. [unreadable] [unreadable]